The mood and behavior changes often associated with aging and the menopause bear directly on the quality of life, and include anxiety, insomnia, fatigue, loss of interest and depression. Estrogen replacement therapy (ERT) has been reported to have a beneficial effect on some of these mood and behavior changes. The mechanism by which estrogen achieves these beneficial effects has not been delineated. Considerable evidence exists that estrogen has a neuropharmacologic effect on adrenergic and serotoninergic function. One specific aim is to relate ERT's effects on mood and behavior to platelet monoamine oxidase (MAO) activity and EEG "driving" responses, noninvasive and easily accessible indices which theoretically relate to central nervous system (CNS) adrenergic and serotoninergic functioning. Establishment of such relationships would give support to the argument that the mood and behavior changes associated with the menopause are secondary to a CNS estrogen deficiency which is most rationally treated by estrogen replacement. ERT is complicated by the need to administer a progestin cyclically with estrogen to counter the risk of endometrial carcinoma. There are reports that the addition of a progestin lessens the beneficial effect of ERT. Another aim of this proposal would be to evaluate the effect of the addition of a progestin to ERT. The aims of this proposal would be accomplished via a double-blind crossover study of 80 menopausal women. Estrogen treatment or placebos would be administered over five 28-day cycles. The hormonal treatment would consist of the administration of estropipate 1.5 mg for 28 days with the addition of norethindrone 1.0 mg the last 10 days of estrogen treatment. Profile of Mood States, Hamilton Scale of Depression, platelet MAO activity and EEG "driving" responses would be assessed on cycle days 9 and 22 of each cycle. Statistical analysis of the data will consist of intercorrelations and repeated measures analyses of variance.